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金纳米粒子嵌入刺激响应型功能糖聚合物:用于协同化学生物动力学疗法治疗癌细胞的潜在材料。

Gold Nanoparticle Embedded Stimuli-Responsive Functional Glycopolymer: A Potential Material for Synergistic Chemo-Photodynamic Therapy of Cancer Cells.

机构信息

Rubber Technology Centre, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India.

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India.

出版信息

Macromol Biosci. 2022 Sep;22(9):e2200069. doi: 10.1002/mabi.202200069. Epub 2022 Jul 19.

DOI:10.1002/mabi.202200069
PMID:35797485
Abstract

Photodynamic therapy has emerged as a noninvasive treatment modality for several types of cancers. However, conventional hydrophobic photosensitizers (PS) suffer from low water solubility and poor tumor-targeting ability. Therefore, PS modified with glycopolymers can offer adequate water solubility, biocompatibility, and tumor-targeting ability due to the presence of multiple sugar units. In this study, a well-defined block copolymer poly(3-O-methacryloyl-d-glucopyranose)-b-poly(2-(4-formylbenzoyloxy)ethylmethacrylate) (PMAG-b-PFBEMA) containing pendant glucose and aldehyde units is synthesized via reversible addition-fragmentation chain transfer polymerization method. A water-soluble PS (toluidine blue O; TBO) and a potent anticancer drug, Doxorubicin (Dox) are introduced to the polymer backbone via acid-labile Schiff-base reaction (PMAG-b-PFBEMA_TBO_Dox). The PMAG-b-PFBEMA_TBO_Dox is then anchored on the surface of gold nanoparticles (AuNPs) via electrostatic interaction. This hybrid system exhibits excellent reactive oxygen species (ROS) generating ability under exposure of 630 nm light-emitting diode along with triggered release of Dox under the acidic pH of tumor cells. The in vitro cytotoxicity study on human breast cancer cell line, MDA MB 231, for this hybrid system shows promising results due to the synergistic effect of ROS and Dox released. Thus, this glycopolymer-based dual (chemo-photodynamic) therapy model can work as potential material for future therapeutics.

摘要

光动力疗法已成为多种癌症的一种非侵入性治疗方法。然而,传统的疏水性光敏剂(PS)存在水溶性差和肿瘤靶向能力差的问题。因此,通过糖基聚合物对 PS 进行修饰可以提供足够的水溶性、生物相容性和肿瘤靶向能力,因为其具有多个糖单元。在这项研究中,通过可逆加成-断裂链转移聚合方法合成了一种含有支链葡萄糖和醛基的两亲性嵌段共聚物聚(3-O-甲基丙烯酰基-d-吡喃葡萄糖)-b-聚(2-(4-甲酰基苯氧基)乙基甲基丙烯酰胺)(PMAG-b-PFBEMA)。将水溶性 PS(甲苯胺蓝 O;TBO)和一种有效的抗癌药物阿霉素(Dox)通过酸不稳定的席夫碱反应引入聚合物主链(PMAG-b-PFBEMA_TBO_Dox)。然后,PMAG-b-PFBEMA_TBO_Dox 通过静电相互作用锚定在金纳米粒子(AuNPs)表面。在 630nm 发光二极管照射下,该杂化系统表现出优异的活性氧(ROS)生成能力,并在肿瘤细胞的酸性 pH 条件下触发 Dox 的释放。该杂化系统对人乳腺癌细胞系 MDA MB 231 的体外细胞毒性研究表明,由于 ROS 和释放的 Dox 的协同作用,该杂化系统具有很好的效果。因此,基于糖基聚合物的双重(化疗-光动力)治疗模型可以作为未来治疗的潜在材料。

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